Mapping strategies towards improved external validity in preclinical translational research

Abstract

Introduction: Translation is about successfully bringing findings from preclinical contexts into the clinic. This transfer is challenging as clinical trials frequently fail despite positive preclinical results. Limited robustness of preclinical research has been marked as one of the drivers of such failures. One suggested solution is to improve the external validity of in vitro and in vivo experiments via a suite of complementary strategies.Areas covered: In this review, we summarize the literature available on different strategies to improve external validity: systematic heterogenization, generalizability tests, multi-batch and multicenter experiments.Expert opinion: The reviewed strategies differentially influence variation in experiments. We argue that applying a combination of these approaches in confirmatory stages of preclinical research putatively increases the chances of success in clinical studies.